Congenital Hepatic Fibrosis as an Early Sign of Presentation of ADPKD

**Background:** Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited polycystic kidney disease, with an incidence of approximately 1:400 to 1:1000. It typically presents in the fourth to fifth decade of life and results from mutations in PKD1 or PKD2. Congenital hepatic fibrosis (CHF) is a rare condition characterized by bile duct distortion and periportal fibrosis, usually associated with autosomal recessive polycystic kidney disease (ARPKD). Only a few cases have linked CHF to ADPKD. This report describes a family with ADPKD in which an 8-year-old boy presented with CHF as the initial manifestation.

**Methods:** This is a single case report with family pedigree analysis. The index patient underwent serial abdominal ultrasonography, liver elastography, upper endoscopy, liver biopsy, and whole exome sequencing. Family members were screened by abdominal ultrasound. The variant identified by whole exome sequencing was confirmed by Sanger sequencing.

**Key Results:** The patient first presented at age 2 with easy bruising on the lower limbs, thrombocytopenia, and mild hepatosplenomegaly. Autoimmune hepatitis, viral hepatitis (CMV, EBV, TORCH), Gaucher disease, and alpha-1 antitrypsin deficiency were excluded. Bone marrow examination was normal. At age 6, liver elastography showed fibrosis at stage F2. At age 8, abdominal ultrasound revealed an enlarged liver (right lobe 130 mm, left lobe 110 mm, caudate lobe 40 mm) and spleen (125 mm). Doppler imaging and upper endoscopy confirmed grade 1 esophageal varices. The last abdominal ultrasound revealed numerous millimetric renal cysts, with the largest cyst in the right kidney measuring 9.2 mm. Laboratory results showed PT 90%, RBC 3.85 × 10^6/µL, Hb 9.2 g/L, and platelet count 77 k/uL. Liver function tests and serum ferritin were normal. Liver biopsy demonstrated severe fibrosis of portal tracts and irregular bile ducts, supporting the diagnosis of CHF. Whole exome sequencing identified a heterozygous pathogenic variant in PKD1: c.6730_673del p.(Ser2244Hisfs*17), which creates a frameshift starting at codon 2244 with a stop codon 16 positions downstream. Family screening revealed that the father and three brothers had bilateral renal cysts with normal liver morphology. The paternal grandmother died of renal disease of unknown cause, and a paternal aunt is on hemodialysis for polycystic kidney disease. Cranial magnetic resonance angiography and echocardiography showed no abnormalities.

**Clinical Implications:** This case demonstrates that CHF with portal hypertension can be the presenting manifestation of ADPKD in early childhood, preceding the development of renal cysts by several years. Clinicians evaluating children with unexplained hepatosplenomegaly and portal hypertension should consider ADPKD in the differential diagnosis, even when kidneys appear normal on initial imaging. A detailed three-generation family history of renal disease is essential. Genetic testing can confirm the diagnosis and guide family screening. Patients with ADPKD and CHF require routine endoscopic surveillance for progression of portal hypertension and variceal bleeding. The finding also underscores that CHF is not pathognomonic for ARPKD and can occur in ADPKD, with important implications for genetic counseling regarding the autosomal dominant inheritance pattern.